Idiopathic (primary) achalasia: a review

Patel et al. Orphanet Journal of Rare Diseases (2015) 10:89 DOI 10.1186/s13023-015-0302-1 REVIEW Open Access Idiopathic (primary) achalasia: a review Dhyanesh A. Patel1, Hannah P. Kim1, Jerry S. Zifodya1 and Michael F. Vaezi2* Abstract Idiopathic achalasia is a primary esophageal motor disorder characterized by loss of esophageal peristalsis and insufficient lower esophageal sphincter relaxation in response to deglutition. Patients with achalasia commonly complain of dysphagia to solids and liquids, bland regurgitation often unresponsive to an adequate trial of proton pump inhibitor, and chest pain. Weight loss is present in many, but not all patients. Although the precise etiology is unknown, it is often thought to be either autoimmune, viral immune, or neurodegenerative. The diagnosis is based on history of the disease, barium esophagogram, and esophageal motility testing. Endoscopic assessment of the gastroesophageal junction and gastric cardia is necessary to rule out malignancy. Newer diagnostic modalities such as high resolution manometry help in predicting treatment response in achalasia based on esophageal pressure topography patterns identifying three phenotypes of achalasia (I-III) and outcome studies suggest better treatment response with types I and II compared to type III. Although achalasia cannot be permanently cured, excellent outcomes are achieved in over 90 % of patients. Current medical and surgical therapeutic options (pneumatic dilation, endoscopic and surgical myotomy, and pharmacologic agents) aim at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Either graded pneumatic dilatation or laparoscopic surgical myotomy with a partial fundoplication are recommended as initial therapy guided by patient age, gender, preference, and local institutional expertise. The prognosis in achalasia patients is excellent. Most patients who are appropriately treated have a normal life expectancy but the disease does recur and the patient may need intermittent treatment. Keywords: Esophagus, Achalasia, Motility disorder, Endoscopic balloon dilatation, Laparoscopic surgery Definition and epidemiology Idiopathic achalasia (ORPHA930) is a primary esophageal motility disorder of unknown etiology characterized manometrically by esophageal aperistalsis and insufficient relaxation of the lower esophageal sphincter (LES) in response to deglutition [1–5]. It is a rare disease with an annual incidence of approximately 2/100,000 and a prevalence rate of 10/100,000 [6]. Studies have shown that incidence and prevalence of the disease are increasing [7, 8] and the peak incidence occurs between 30 and 60 years of age [7]. Achalasia was first described and termed by Sir Thomas Willis in 1674, when he suggested that the disease is due to the loss of normal inhibition in the distal esophagus [9]. Since then, the development of new diagnostic techniques stimulated new ideas about the etiology and pathophysiology of the disease leading * Correspondence: 2 Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA Full list of author information is available at the end of the article to various theories in identifying the nature of motor disturbances in esophageal regions. However, the initiating cause is still unclear [3, 9, 10]. In this review article we provide current insight on the pathogenesis, etiology, diagnosis, and treatment options for this motor disorder of the esophagus. Clinical description Achalasia is one of the most investigated motor disorders of the esophagus [4, 10]. The disease can occur at any age but it is usually diagnosed between 30 and 60 years. Progressive dysphagia to solids followed by liquids (82 %-100 %) is the first clinical symptom of achalasia [11]. Although dysphagia can occur in patients with other esophageal motility disorders, this symptom is most characteristic of achalasia and strongly suggests the diagnosis. Regurgitation not responding to adequate proton pump inhibitor (PPI) therapy and weight loss can be seen in 30 % to 90 % of patients. Regurgitation of © 2015 Patel et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Patel et al. Orphanet Journal of Rare Diseases (2015) 10:89 material retained in the dilated esophagus, especially during supine position at night, may lead to aspiration. There is no universal definition for “adequate” PPI therapy, however, based on recent gastro-esophageal reflux disease (GERD) guidelines, it has been taken to constitute ensuring compliance, optimal dosing, changing to a different PPI, and possibly BID dosing [12]. Chest pain is another presenting symptom of achalasia (17 %-95 %). The occurrence of this symptom is unrelated to the LES pressure [4, 11]. Chest pain has been found to be more frequent in younger patients and in female patients who have achalasia [4, 13–15]. In addition, 40 % of patients with achalasia report occurrence of at least one respiratory symptom daily, including cough (37 %), hoarseness (21 %), wheezing (15 %), shortness of breath (10 %), and sore throat (12 %) [16]. Heartburn, the main symptom of GERD, may also occur infrequently (27 %-42 %) in achalasia patients. The mean LES pressure in patients with achalasia who experience heartburn has been reported to be significantly lower than that in patients without heartburn [17]. Weight loss (usually between 5 and 10 kg) is present in most but not all patients. Difficulty belching has also been reported in up to 85 % of the patients, and is due to a defect in relaxation of the upper esophageal sphincter in these patients [1, 18]. Etiology The distal esophageal wall and LES are innervated by postganglionic neurons, consisting of excitatory and inhibitory neurons. The excitatory neurons release acetylcholine while the inhibitory neurons release nitric oxide (NO) and vasoactive intestinal polypeptide (VIP), resulting in esophageal and LES contractions and relaxations, respectively [3]. The NO and VIP releasing inhibitory neurons are the target in idiopathic achalasia. Loss of these inhibitory neurons due to either intrinsic or extrinsic causes will result in the manometric consequence of failure of LES relaxation and loss of esophageal peristalsis [3, 4, 19]. Several studies on humans and animals [20, 21] have suggested that extrinsic causes such as lesions located in the central nervous system (CNS) may produce manometric findings of achalasia. Abnormalities of the vagal nerve fibers outside the (...truncated)